While obvious birth defects have received a good deal of attention, subtle differences at birth and their long-term effects have not. Marginal B12 intake during gestation has been correlated with such effects in rodents. In this study of detailed analysis of B12 placental transport will be made. The proposed investigations are comprised of four major parts: (1) Characterization of the binding of transcobalamin II-B12 to trophoblast cell membranes. A study of the parameters which govern the binding of the complex to the membrane is underway. A specific binding protein (? receptor) has been iientified in the membrane; solubilization and purification of this binding protein is anticipated. (2) Subcellular distribution of B12 in placenta. At given times after intravenous labeled B12 administration rodents will be sacrificed and the placental tissues fractionated and counted for radioactivity. In this way the time-dependent accumulation of B12 in subcellular compartments will be evaluated. An analogous in vitro analysis will be performed with intact human trophoblast cells maintained for varying time intervals in physiological incubation buffer after a brief exposure to labeled B12 bound to transcobalamin II. (3) B12 binding and its time-dependent subcellular distribution by human trophoblast in various pathological states. Using trophoblast membrane preparations and intact trophoblast cells from mothers in whom an abnormality has occurred during gestation or at birth, we will compare these parameters to "normal" trophoblast. (4) Vitamin B12 as a vehicle for other nutrients and drugs. A compound containing B12 and a second molecule (which alone does not pass the placenta) will be designed. We will attempt to use the B12 transport system to allow the second molecule to pass to the fetal circulation.